Finding an "Achilles' heel" of cancer: the role of glucose and glutamine metabolism in the survival of transformed cells.

Multiple lines of evidence indicate that the process of tumorigenesis is often associated with altered metabolism of two major nutrients, glucose and glutamine. These two nutrients are engaged in multiple metabolic pathways that can be required for cell viability. The roles of glucose and glutamine in the survival of transformed cells both in vitro and in vivo have been separately evaluated in various cell systems, and glucose as the major cellular energy source has received most of the attention. At the same time, data suggests that the inclusion of glucose and glutamine into specific metabolic pathways and cellular sensitivity to the availability of either of these nutrients depends on the cell origin and the combination and nature of transforming events. Exploiting cell metabolism to develop selective cancer therapeutics requires consideration of these factors and evaluation of the requirement of glucose and glutamine metabolism for survival of different transformed cells. Here we discuss possible molecular mechanisms underlying oncogene-induced sensitivity to deprivation of these nutrients.